Polyester-based nanoparticles (NPs) are among the most adopted drug delivery systems developed so far. This is mainly due to their ability to increase the bioavailability of the loaded therapeutics, to prevent the adverse effects often associated with their use, and to eliminate the toxic excipients necessary to formulate them. In addition, these NPs are biodegradable under physiological conditions thus avoiding the polymer accumulation in the body. However, the complexity in the formulation and storage hampers the cost-effective use of these formulations reducing their availability among the patient population. In addition, the manifold drugs available on the market, characterized by different chemical structures and charges, impose the continuous optimization of different delivery systems for their efficient formulation. Therefore, tunable NPs able to encapsulate different drugs with high loading efficiencies and to modulate their release after administration are urgently needed. In this work, a method to formulate different drugs directly at the point of care using only a syringe and starting from preformed NPs has been developed. Highly tunable zwitterionic NPs have been synthesized via the combination of ring opening polymerization and reversible addition–fragmentation chain transfer emulsion polymerization and then used to load paclitaxel, doxorubicin, or ibuprofen with high efficiency. The controlled release of such therapeutics has been achieved by tuning the characteristics of the NPs, in particular by the addition of charged groups.

Reactive microgliosis is a pathological hallmark that accompanies neuronal demise in many neurodegenerative diseases, ranging from acute brain/spinal cord injuries to chronic diseases, such as amyotrophic lateral sclerosis (ALS), Alzheimer’s disease (AD) and age-related dementia. One strategy to assess and monitor microgliosis is to use positron emission tomography (PET) by exploiting radioligands selective for the 18 kDa translocator protein (TSPO) which is highly upregulated in the brain in pathological conditions. Several TSPO ligands have been developed and validated, so far. Among these, PBR28 has been widely adopted for PET imaging at both preclinical and clinical levels, thanks to its high brain penetration and high selectivity. For this reason, PBR28 represents a good candidate for functionalization strategies, where this ligand could be exploited to drive selective targeting of TSPO-expressing cells. Since the PBR28 structure lacks functional moieties that could be exploited for derivatization, in this work we explored a synthetic pathway for the synthesis of a PBR28 derivative carrying an alkyne group (PBR-alkyne), enabling the fast conjugation of the ligand through azide-alkyne cycloaddition, also known as click-chemistry. As a proof of concept, we demonstrated in silico that the derivatized PBR28 ligand maintains the capability to fit into the TSPO binding pocked, and we successfully exploited PBR-alkyne to decorate zwitterionic biodegradable polymer nanoparticles (NPs) resulting in efficient internalization in cultured microglia-like cell lines.

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Today, neurodegenerative diseases are affecting more and more individuals. A typical therapeutic target to treat the progression of the symptoms related to these diseases is the proinflammatory microglia. Diapocynin, the dimeric version of apocynin, is often the drug of choice. However, suitable carriers for its controlled delivery are currently lacking in the clinics. In fact, its high hydrophilicity hampers the development of a formulation enabling its sustained release in a biological environment. In this work, the possibility of modifying diapocynin is explored in order to synthesize a prodrug that can be chemically incorporated into biodegradable zwitterionic polymer nanoparticles (NPs). These NPs are synthesized via combination of ring opening polymerization and reversible addition-fragmentation chain transfer (RAFT) polymerization, allowing the incorporation of the desired number of diapocynin units into the carrier and thus to set the drug dosage a priori. The chemical binding of diapocynin avoids its premature release compared to its physical loading inside similar nanovectors. With this strategy, sustained diapocynin release can be achieved for more than 9 days, thus paving the way to a therapy with low number of repeated administrations.

Tailor-made materials for biomedical applications can be constructed with different building blocks to confer multiple functions on one platform. Here, we demonstrate the facile synthesis of magnetite-biodegradable polymer nanocomposites combining superparamagnetism with the possibility of loading and controlling the release of a lipophilic drug. The magnetite nanoparticles were synthesized by reduction–precipitation and used as nuclei to grow a biodegradable zwitterionic shell. The copolymer used for this scope comprises a hydrophobic block made of a biodegradable ε-caprolactone-based macromonomer (CL n ) with three different degrees of polymerization (DP n , n = 3, 5, and 7) obtained by ring-opening polymerization (ROP). Dopamine molecules were attached to the end of this CL n oligomer (CL n Dopa), conferring a specific affinity for the magnetite surface. A hydrophilic zwitterionic poly(2-methacryloyloxyethyl phosphorylcholine) block (PMPC) was included by reversible addition–fragmentation chain transfer (RAFT) polymerization to add colloidal stability and water dispersibility to the copolymer. This PMPC was chain-extended with CL n Dopa via RAFT polymerization targeting four different DP m (m = 10, 20, 30, and 40), resulting in a library of 12 copolymers. A facile nanoprecipitation process produced copolymer nanoparticles and copolymer-coated magnetite nanostructures. Physicochemical characterization confirmed the inorganic–organic composite nature. The copolymer-coated magnetic materials showed water stability, superparamagnetic behavior, and appropriate hyperthermic ability under an alternate magnetic field. Biological assays using HeLa cells showed high biocompatibility and efficient nanoparticle uptake. In addition, a sustained release of dexamethasone, used as a model drug encapsulated in the polymer shell, and local heating as a dual functional material could be accessed.